Gopal Basu

Interactions between thyroid disorders and kidney disease

There are several interactions between thyroid and kidney functions in each other organs disease states. Thyroid hormones affect renal development and physiology. Thyroid hormones have pre-renal and intrinsic renal effects by which they increase the renal blood flow and the glomerular filtration rate (GFR). Hypothyroidism is associated with reduced GFR and hyperthyroidism results in increased GFR as well as increased renin – angiotensin – aldosterone activation. Chronic kidney disease (CKD) is characterized by a low T3 syndrome which is now considered a part of an atypical nonthyroidal illness. CKD patients also have increased incidence of primary hypothyroidism and subclinical hypothyroidism. The physiological benefits of a hypothyroid state in CKD, and the risk of CKD progression with hyperthyroidism emphasize on a conservative approach in the treatment of thyroid hormone abnormalities in CKD. Thyroid dysfunction is also associated with glomerulonephritis often by a common autoimmune etiology. Several drugs could affect both thyroid and kidney functions. There are few described interactions between thyroid and renal malignancies. A detailed knowledge of all these interactions is important for both the nephrologists and endocrinologists for optimal management of the patient.

Acute kidney injury in tropical acute febrile illness in a tertiary care centre—RIFLE criteria validation

BACKGROUND Acute febrile illnesses are a common cause of tropical acute kidney injury (AKI). The incidence and severity of AKI in tropical febrile illnesses and validity of RIFLE classification are unclear. METHODS Consecutive adult inpatients of a tertiary hospital in southern India with tropical acute febrile illness between January 2007 and January 2008 were prospectively studied for the incidence and severity of AKI based on RIFLE classification and its association with mortality and dialysis requirement. RESULTS The 367 patients (mean age 39.7±16.9 years; 60% males) with tropical acute febrile illness due to scrub typhus (51.2%), falciparum malaria (10.4%), enteric fever (8.7%), dengue (7.6%), mixed malaria (6.5%), leptospirosis (3.3%), undifferentiated acute febrile illness (8.4%) and others (3.8%) (spotted fever, vivax malaria and Hantaan virus infection) had an overall mortality rate of 12.3%. The incidence of AKI was 41.1%; of which, 17.4%, 9.3% and 14.4% were in the Risk, Injury and Failure classes, respectively. Of the patients, 7.9% required dialysis. Among the Risk, Injury and Failure groups, there was an incremental risk of mortality (OR 6.9, 20.2 and 25.6; P<0.001) and dialysis requirement (OR 3.4, 28.8 and 178.8; P<0.001). CONCLUSIONS The incidence of AKI in the common tropical acute febrile illnesses in our study such as scrub typhus, falciparum malaria, enteric fever, dengue and leptospirosis is 41.1%. RIFLE classification is valid and applicable in AKI related to tropical acute febrile illnesses, with an incremental risk of mortality and dialysis requirement.

A model for human leukocyte antigen-matched donor-swap transplantation in India.

Background. In developing countries such as India, extending donor-swap transplantation (DSTx) to human leukocyte antigen (HLA)-mismatched patient-donor pairs would increase well-matched living donor kidney transplantation rates, resulting in use of less immunosuppression and less expenses, lower infective morbidity, and better survival. A model for DSTx based on HLA matching is presented. Methods. Consecutive HLA class 1 antigen (A, B) tests of prospective renal allograft recipients and their related donors, performed at a single center in India was analyzed retrospectively using an HLA matching program to determine the proportion of prospective recipients with poorly matched related donors who could have benefited by DSTx based on HLA matching. Results. Over the past 17.5 years, 2,129 prospective renal allograft recipients and 2,890 donors were tested for HLA class I (A and B) antigens. Of the prospective recipients, 33% did not have well-matched donors (defined as blood group compatible and sharing ≥2 of 4 HLA class I antigens). Among such recipients, 19.2% could have found a well-matched donor-swap pair within a year at a single center. This number would increase to 38% if four major national centers were involved with a shared HLA registry. Conclusions. Nearly 40% of prospective recipients without well-matched donors would find a donor-swap pair based on HLA matching within a year, with coordination among four national centers and a shared HLA registry, increasing the well-matched living donor renal transplant rates and improving transplant outcomes. This finding is relevant in the context of Indian government amending the Transplantation of Human Organs Act to encourage DSTx.

Leflunomide with low-dose everolimus for treatment of Kaposi’s sarcoma in a renal allograft recipient

Current treatment of Kaposis sarcoma is reduction of immunosuppression with or without addition of mammalian target of rapamycin inhibitors (mTORi). Akt signalling plays a central role in oncogenesis of Kaposis sarcoma. We describe a case of multifocal Kaposis sarcoma in a renal allograft recipient, which showed unsatisfactory early response to immunosuppression reduction along with everolimus therapy but completely resolved after adding leflunomide. mTORi impair Kaposis sarcoma oncogenesis by inhibiting mTOR downstream from the Akt signalling. Leflunomide inhibits Akt phosphorylation. This synergistic effect may be beneficial in treatment of Kaposi sarcoma and needs to be explored in trials.

Percutaneous continuous ambulatory peritoneal dialysis (CAPD) catheter insertion--a preferred option for developing countries.

Continuous ambulatory peritoneal dialysis (CAPD) as a modality of renal replacement therapy in patients with chronic kidney disease stage 5 (CKD 5) has the advantage of being a home-based therapy and is a preferred option in patients with inadequate access to haemodialysis and transplantation facilities and in those infected with HIV and other blood-borne viruses. While open surgical CAPD catheter placement has been the conventional mainstay of access placement, percutaneous techniques are being increasingly used with similar success rates. We report our experience over the past two years with blind insertion of the swan neck percutaneous double-cuffed Tenckhoff CAPD catheter using a trocar. There was considerable decrease in hospital stay and surgical costs. There was only one major complication of injury to the jejunal mesenteric artery requiring emergency laparotomy in one patient. In three patients, drain of peritoneal fluid was inadequate, presumably due to omental wrapping around the in-dwelling catheter, and required surgical removal of the omentum.

Tuberculosis in a renal allograft recipient presenting with intussusception

Extra-pulmonary tuberculosis (TB) is more common in renal allograft recipients and may present with dissemination or an atypical features. We report a renal allograft recipient with intestinal TB presenting 3 years after transplantation with persistent fever, weight loss, diarrhea, abdominal pain and mass in the abdomen with intestinal obstruction. He was diagnosed to be having an ileocolic intussusception which on resection showed a granulomatous inflammation with presence of acid-fast bacilli (AFB) typical of Mycobacterium tuberculosis. In addition, AFB was detected in the tracheal aspirate, indicating dissemination. He received anti-TB therapy (ATT) from the fourth postoperative day. However, he developed a probable immune reconstitution inflammatory syndrome (IRIS) with multiorgan failure and died on 11th postoperative day. This is the first report of intestinal TB presenting as intussusception in a renal allograft recipient. The development of IRIS after starting ATT is rare in renal allograft recipients. This report highlights the need for a high index of suspicion for diagnosing TB early among renal transplant recipients and the therapeutic dilemma with overwhelming infection and development of IRIS upon reduction of immunosuppression and starting ATT.

Trichosporon Surgical Wound Infection in a Renal Allograft Recipient Successfully Treated With Voriconazole

A 39-year-old chronic kidney disease patient underwent a preemptive renal transplantation in November 2009. His native kidney disease was unknown (biopsy performed in 2006 showed diffuse global sclerosis). He reached end stage in 2009 and after that he was worked up for transplantation. He was not a diabetic and did not have any other comorbidity. He did not receive any immunosuppression before renal transplantation. His wife donated the kidney. His immunosuppression included Basiliximab (two doses) for induction along with prednisolone, tacrolimus, and mycophenolate sodium for maintenance. He had a prolonged warm ischemia time because of difficulty in donor nephrectomy. After surgery, he had a slow recovery in renal function for which a graft biopsy was performed on 4th postoperative day. It showed acute tubular necrosis. Tacrolimus levels were found to be high (13 ng/mL), and hence the dose was reduced. Because renal recovery continued to be slow, a second renal biopsy was performed after a week, which showed cortical necrosis at the upper pole. Without any specific intervention, renal function slowly improved to attain a nadir creatinine of 1.4 mg/dL. Dose titration of tacrolimus and mycophenolate sodium was performed in this period with therapeutic drug monitoring. In the postoperative period, he had received ciprofloxacin as treatment for lower respiratory infection and there were no other infective episodes. After suture removal, he was found to have pus discharge from the surgical wound site. A pus swab for culture grew Trichosporon species. It was confirmed by a second culture. An ultrasonogram revealed a small subcutaneous collection. Surgeons considered exploration to be unnecessary and wanted daily dressings only. A small noncompressing lymphocele was also noted near the lower pole of the graft kidney. Imaging studies excluded involvement of other organs. He did not have neutropenia. Antifungal therapy in voriconazole was begun at standard doses (400 mg twice daily on day 1 followed by 200 mg twice daily). Tacrolimus dose was decreased based on new trough levels. Mycophenolate area under the curve was found to be high, and the dose was dropped. He showed response to the treatment with clearing of the discharge. The wound healed within 2 weeks and the subcutaneous collection resolved. Voriconazole was continued for 4 weeks and stopped. His renal function remains stable and the wound is healthy.

Non‑O1, non‑O139 Vibrio cholerae sepsis in a patient with nephrotic syndrome

Non-O1, non-O139 Vibrio cholerae is an encapsulated bacterium, ubiquitous in the marine environment and generally considered to be non-pathogenic. However, it is known to cause diarrheal illness, wound infection, and bacteremia in immunocompromised hosts. Here we have describe non-O1, non-O139 V. cholerae sepsis in a patient with nephrotic syndrome following exposure to sea-water. Interestingly, the exposure occurred remotely 4 months prior to the onset of nephrotic syndrome. The occurrence of florid sepsis after a prolonged interval from the time of exposure is peculiar and raises the possibility of an association between occult Vibrio sepsis and nephrotic syndrome.

Adefovir nephrotoxicity in a renal allograft recipient

Adefovir dipivoxil, an oral prodrug of adefovir, is used in the treatment of lamivudine-resistant hepatitis B virus (HBV) infection. Nephrotoxicity manifesting as proximal renal tubular dysfunction and acute tubular necrosis (ATN) were commonly reported in the past, when higher doses were used for the treatment of human immunodeficiency virus infection. However, nephrotoxicity is rare at lower doses that are currently recommended for the treatment of HBV infection. A 31-year-old female was detected to be hepatitis B surface antigen positive months after a kidney transplant. The patient was initiated on lamivudine, but developed resistance after 1 year of treatment, at which time low-dose adefovir was added. The patient developed renal allograft dysfunction after 10 months of starting adefovir. Serum creatinine increased from 1.1 mg/dl to 1.9 mg/dl, along with progressively increasing sub-nephrotic proteinuria. Renal allograft biopsy revealed features of ATN. After discontinuation of adefovir, proteinuria resolved and renal dysfunction improved slowly over the next 2 years. Adefovir-induced nephrotoxicity, although uncommon at lower doses, needs to be considered in the differential diagnosis of renal dysfunction and sub-nephrotic proteinuria occurring in patients receiving adefovir for prolonged periods.

Profile of incident chronic kidney disease related-mineral bone disorders in chronic kidney disease Stage 4 and 5: A hospital based cross-sectional survey.

Chronic kidney disease related-mineral bone disorder (CKD-MBD) has been poorly studied in pre-dialysis Indian CKD patients. We aimed to study the clinical, biochemical and extra skeletal manifestations of untreated CKD-MBD in pre-dialysis Stage 4 and 5 CKD patients attending nephrology out-patient clinic at a tertiary care hospital in South India. A hospital based cross-sectional survey including, demographic profile, history of CKD-MBD symptoms, measurement of serum calcium, phosphate, parathyroid hormone, 25 hydroxy vitamin D (25(OH) D) and alkaline phosphatase; lateral abdominal X-rays for abdominal aortic calcification (AAC) and echocardiography for valvular calcification (VC) was carried out. Of the 710 patients surveyed, 45% had no CKD-MBD related symptom. Prevalence of hypocalcemia, hyperphosphatemia, hyperparathyroidism (>150 pg/mL) and 25(OH) D levels <30 ng/mL was 66.3%, 59%, 89.3% and 74.7% respectively. Echocardiography was carried out in 471 patients; 96% of whom had VC (calcification score ≥1). Patients with VC were older and had lower 25(OH) D levels than those without. Lateral abdominal X-rays were obtained in 558 patients, 6.8% of whom were found to have AAC, which was associated with older age. Indian patients with incident CKD-MBD have a high prevalence of hypocalcemia, 25(OH) D deficiency and VC even prior to initiating dialysis while AAC does not appear to be common. The association between 25(OH) D deficiency and VC needs further exploration.